EP-A-1 230 935 describes the introduction of drug molecules into polysaccharides, which is non-uniform, however, with respect to the frequency of drug molecules bound per polysaccharide molecule and the binding sites of such molecules. Thus, it can be observed that a large number of smaller drug molecules are bound to single polysaccharide molecules while others remain substantially unoccupied. On the one hand, this substantially reduces the yield of desired coupling products, and on the other hand, it is very tedious to separate the desired coupling products, i.e. the polysaccharide compounds with the desired number of introduced molecules, from undesired coupling products. If coupling reactions are performed in which the drugs are to be bound into the starch molecule by linker molecules, undesirable cross-linking of the polysaccharides themselves may occur.
It is possible to avoid such cross-linking in the special case where exactly one molecule of the medicinally active substance is to be bound to one polysaccharide molecule each. Here, it is possible to bind this medicinal substance to the terminal aldehyde group of the terminal glucose monomer of starch as described in DE 102 09 822 A1.
However, when several drug molecules are bound via polyvalent linker molecules, the regioselective controllability of the binding or substitution is lost. A corresponding bonding of medicinal substances with hydroxyethyl starch (HES) in terms of a HESylation of active substances, i.e., the chemical coupling of different HES variants to medicinal substances, is disclosed in DE 101 12 825 A1, the course of the reaction in an aqueous solution being described.
In the mentioned process, either one medicinally active molecule is bound to exactly one terminal aldehyde group, or an unknown number of medicinally active molecules is non-specifically bound to the hydroxyethyl starch covalently via linkers.
In hydroxyethyl starch as in the majority of drags, hydroxy groups are primarily available for bonding. Bifunctional carboxylic acids may be used as linkers. It is known that dicarboxylic acid chlorides act as cross-linking agents for polysaccharides. When esterified with dicarboxylic acid chlorides, for example, malonic acid dichloride, a pronounced mutual cross-linking of the polysaccharides occurs in addition to the desired bonding of the medicinally active substance into the polysaccharide through an ester linkage.
By bonding medicinal substances to hydroxyethyl starch, such medicinal substances can be hydrophilized. In addition, the drug-HES compound obtained is colloid-osmotically active, like hydroxyethyl starch itself.
However, further utilizable physico-chemical principles of action are desirable for the control of and specific influence on the activity of bound medicinal substances.
Accordingly, it is the object of the invention to provide a compound suitable as a carrier for medicinal substances and a compound derived therefrom that carries medicinal substances, wherein said compounds additionally have good water solubility, a specific charge pattern with both positive and negative charges (dipole), a low allergenic activity and complete degradability.